2-(2′,6′-Dioxopiperidin-3′-yl)isoindoles, Formula A shown below, are derivatives of thalidomide and are currently being studied as immunomodulators.
The compounds of the above formula, including N-((2-(2′,6′-dioxopiperidin-3′-yl)-1,3-dioxoisoindolin-4-yl)methyl)cyclopropanecarboxamide, are described in U.S. Pat. Nos. 7,091,353; 7,189,740; 7,393,863; and, 7,576,104; the contents of which are incorporated herein by reference.
The compounds of Formula A, because of the asymmetric 3′ carbon on the glutarimide ring (2′,6′-dioxopiperidinyl ring), is a racemic mixture of R and S stereoisomers. The hydrogen at the 3′ position is acidic due to the presence of the adjacent carbonyl moiety, thereby making it difficult to separate the two stereoisomers and difficult to determine if one of the stereoisomers is superior to the other.
WO2010/093604 describes isotopologues of thalidomide but does not describe deuteration at the asymmetric carbon of its glutarimide ring.
WO2010/093434 describes isotopologues of lenalidomide but does not describe deuteration at the asymmetric carbon of its glutarimide ring.
WO2008/027542 and WO2009/145899 describe 5-substituted isoindolines, but neither describes deuteration at the asymmetric carbon of its glutarimide ring. The disclosures of these applications are incorporated herein by reference.
WO2008/033567 describes N-methylaminomethyl isoindoles, but does not describe deuteration at the asymmetric carbon of its glutarimide ring. The disclosure of this application is incorporated herein by reference.
WO2008/115516, WO2010/053732, and WO2011/100380 describe 4′-O-substituted isoindolines, isoindolines, and arylmethoxy isoindolines, respectively, but do not describe deuteration at the asymmetric carbon of their respective glutarimide rings. The disclosures of these applications are incorporated herein by reference.
Since 2-(2′,6′-dioxopiperidin-3′-yl)isoindoles are known and useful pharmaceutical compounds, it is desirable to discover novel derivatives thereof.